EP0966671B1 - Fiberoptischer sensor mit kodierten mikrokugeln - Google Patents
Fiberoptischer sensor mit kodierten mikrokugeln Download PDFInfo
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- EP0966671B1 EP0966671B1 EP98910397A EP98910397A EP0966671B1 EP 0966671 B1 EP0966671 B1 EP 0966671B1 EP 98910397 A EP98910397 A EP 98910397A EP 98910397 A EP98910397 A EP 98910397A EP 0966671 B1 EP0966671 B1 EP 0966671B1
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- Prior art keywords
- microspheres
- wells
- optical
- optical fiber
- microsphere
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Electro-optical investigation, e.g. flow cytometers
- G01N15/1434—Electro-optical investigation, e.g. flow cytometers using an analyser being characterised by its optical arrangement
- G01N2015/1438—Using two lasers in succession
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/645—Specially adapted constructive features of fluorimeters
- G01N2021/6484—Optical fibres
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N2021/7769—Measurement method of reaction-produced change in sensor
- G01N2021/7786—Fluorescence
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
- G01N2035/0097—Control arrangements for automatic analysers monitoring reactions as a function of time
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S359/00—Optical: systems and elements
- Y10S359/90—Methods
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/808—Optical sensing apparatus
Definitions
- Enzyme-based microsphere sensors have also been demonstrated and could be manifest on microspheres. As shown in Table IV, examples include: Table IV SENSOR TARGET CHEMICAL FUNCTIONALITY Glucose Sensor glucose oxidase (enz.) + 0 2 -sensitive dye (see Table I) Penicillin Sensor penicillinase (enz.) + pH-sensitive dye (see Table I) Urea Sensor urease (enz.) + pH-sensitive dye (see Table I) Acetylcholine Sensor acetylcholinesterase (enz.) + pH-sensitive dye (see Table I)
- Figs. 7A and 7B show polymer coated microspheres 12 in wells 250 after their initial placement and then after tapping and exposure to air pulses.
- Figs. 7A and 7B illustrate that there is no appreciable loss of microspheres from the wells due to mechanical agitation even without a specific fixing technique. This effect is probably due to electrostatic forces between the microspheres and the optical fibers. These forces tend to bind the microspheres within the wells. Thus, in most environments, it may be unnecessary to use any chemical or mechanical fixation for the microspheres.
- Alkaline phosphatase Target substrate fluorescein diphosphate (FDP) Reported dye ratio: 1:1 ratio of DiIC:TRC, where DiIC is 1,1',3,3,3',3'-hexamethyl-indodicarbocyanine iodide and TRC is Texas Red cadaverine
- FDP fluorescein diphosphate
Claims (16)
- Sensor, umfassend eine Gesamtheit von Mikrokugeln, die Sub-Gesamtheiten umfassen, wobei jede Sub-Gesamtheit eine unterschiedliche chemische Funktionalität (12) und eine optische Signatur aufweist, die verwendet werden kann, um die chemische Funktionalität zu identifizieren, dadurch gekennzeichnet, dass der Sensor ferner ein optisches Faserbündel (202) umfasst, das ein Eingangsende (212) aufweist, wobei das Eingangsende (212) eine Vielzahl an Vertiefungen (250) umfasst, wobei jede Vertiefung (250) der Vielzahl an Vertiefungen (250) an einer separaten optischen Faser (252) des optischen Faserbündels (202) angeordnet ist, und wobei die Gesamtheit von Mikrokugeln (10) am Eingangsende des optischen Faserbündels (212) so verteilt ist, dass separate Vertiefungen (250) der Vielzahl an Vertiefungen (250) eine einzige Mikrokugel (10) enthalten.
- Sensor nach Anspruch 1, worin die optische Signatur durch zumindest einen Farbstoff (14) erzeugt wird, der aus der aus Fluorophoren, Chromophoren und Phosphoren bestehenden Gruppe ausgewählt ist.
- Sensor nach Anspruch 1 oder 2, worin die optische Signatur durch zumindest einen fluoreszenten Farbstoff (14) erzeugt wird.
- Sensor nach einem der Ansprüche 1 bis 3, worin die optische Signatur durch ein Verhältnis von zumindest zwei oder mehreren fluoreszenten Farbstoffen (14) erzeugt wird.
- Sensor nach einem der Ansprüche 1 bis 4, worin die chemische Funktionalität (12) aus der aus Nucleinsäuren, Antikörpern und Enzymen bestehenden Gruppe ausgewählt ist.
- Sensor nach einem der vorangegangenen Ansprüche, ferner umfassend eine Lichtquelle (224).
- Sensor nach einem der vorangegangenen Ansprüche, ferner umfassend eine CCD (Charge-Coupled Device)-Kamera.
- Sensor nach einem der vorangegangenen Ansprüche, worin die optische Signatur durch eine oder mehrere Farbstoffe (14) erzeugt wird, die in den Mikrokugeln eingeschlossen sind.
- Verfahren zur Bestimmung des Vorhandenseins eines Analyts, umfassend:das Kontaktieren eines Sensors nach einem der vorangegangenen Ansprüche mit der Probe unddas Bestimmen, ob es zu einer Veränderung der optischen Signatur an einer Mikrokugel kommt, die eine chemische Funktionalität aufweist, die auf diesen Analyt ausgerichtet ist, wobei die Veränderung das Vorhandensein des Analyts anzeigt.
- Verfahren nach Anspruch 9, worin der Analyt eine Nucleinsäure ist.
- Verfahren zur Herstellung eines Sensors, umfassend:die Bereitstellung eines optischen Faserbündels, das ein Eingangsende umfasst, wobei das Eingangsende eine Vielzahl an Vertiefungen umfasst, wobei jede Vertiefung der Vielzahl an Vertiefungen an einer separaten optischen Faser des optischen Faserbündels angeordnet ist, unddas Verteilen einer Gesamtheit von Mikrokugeln am Eingangsende des optischen Faserbündels, sodass die separaten Vertiefungen der Vielzahl an Vertiefungen eine einzige Mikrokugel aufweisen, wobei die Mikrokugeln der Gesamtheit von Mikrokugeln Sub-Gesamtheiten umfassen, wobei jede Sub-Gesamtheit eine unterschiedliche chemische Funktionalität und eine optische Signatur aufweist, die verwendet werden kann, um die chemische Funktionalität zu identifizieren.
- Verfahren nach Anspruch 11, worin die Bereitstellung eines optischen Faserbündels ferner die Ausbildung der Vielzahl an Vertiefungen umfasst.
- Verfahren nach Anspruch 12, worin die Ausbildung das Ätzen der Kerne der optischen Fasern des optischen Faserbündels umfasst.
- Verfahren nach Anspruch 13, worin das Verteilen der Gesamtheit von Mikrokugeln die aufeinanderfolgende Zugabe der Sub-Gesamtheiten zu den Vertiefungen umfasst.
- Verfahren nach einem der Ansprüche 11 bis 14, ferner umfassend die Herstellung von Mikrokugeln der Gesamtheit von Mikrokugeln durch die Bindung der chemischen Funktionalität an diese.
- Verfahren nach einem der Ansprüche 11 bis 15, ferner umfassend die Herstellung von Mikrokugeln der Gesamtheit von Mikrokugeln durch die Zuordnung der optischen Signatur zu dieser.
Priority Applications (1)
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EP20080012004 EP2006665B1 (de) | 1997-03-14 | 1998-03-13 | Faseroptischer Sensor mit Enzym tragenden Mikrosphären |
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US818199 | 1997-03-14 | ||
US08/818,199 US6023540A (en) | 1997-03-14 | 1997-03-14 | Fiber optic sensor with encoded microspheres |
PCT/US1998/005025 WO1998040726A1 (en) | 1997-03-14 | 1998-03-13 | Fiber optic sensor with encoded microspheres |
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EP20080012004 Division EP2006665B1 (de) | 1997-03-14 | 1998-03-13 | Faseroptischer Sensor mit Enzym tragenden Mikrosphären |
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EP98910397A Expired - Lifetime EP0966671B1 (de) | 1997-03-14 | 1998-03-13 | Fiberoptischer sensor mit kodierten mikrokugeln |
EP20080012004 Expired - Lifetime EP2006665B1 (de) | 1997-03-14 | 1998-03-13 | Faseroptischer Sensor mit Enzym tragenden Mikrosphären |
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US (3) | US6023540A (de) |
EP (2) | EP0966671B1 (de) |
JP (1) | JP3886161B2 (de) |
AT (1) | ATE408138T1 (de) |
AU (1) | AU746365B2 (de) |
CA (1) | CA2283742C (de) |
DE (1) | DE69839990D1 (de) |
WO (1) | WO1998040726A1 (de) |
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1998
- 1998-03-13 WO PCT/US1998/005025 patent/WO1998040726A1/en active IP Right Grant
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- 1998-03-13 EP EP98910397A patent/EP0966671B1/de not_active Expired - Lifetime
- 1998-03-13 AU AU64648/98A patent/AU746365B2/en not_active Expired
- 1998-03-13 JP JP53987498A patent/JP3886161B2/ja not_active Expired - Lifetime
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- 1998-03-13 DE DE69839990T patent/DE69839990D1/de not_active Expired - Lifetime
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1999
- 1999-11-29 US US09/450,829 patent/US6266459B1/en not_active Expired - Lifetime
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2001
- 2001-04-20 US US09/840,012 patent/US20020122612A1/en not_active Abandoned
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US6266459B1 (en) | 2001-07-24 |
EP2006665B1 (de) | 2015-04-22 |
CA2283742A1 (en) | 1998-09-17 |
EP2006665A2 (de) | 2008-12-24 |
JP3886161B2 (ja) | 2007-02-28 |
EP2006665A3 (de) | 2009-04-15 |
DE69839990D1 (de) | 2008-10-23 |
ATE408138T1 (de) | 2008-09-15 |
WO1998040726A1 (en) | 1998-09-17 |
AU746365B2 (en) | 2002-04-18 |
US20020122612A1 (en) | 2002-09-05 |
AU6464898A (en) | 1998-09-29 |
JP2001524208A (ja) | 2001-11-27 |
EP0966671A1 (de) | 1999-12-29 |
US6023540A (en) | 2000-02-08 |
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